Biomedical subjects

A Fischer

Publications and source records attributed to A Fischer.

At least 37 records · Page 2Linked to original sources

PubMed2006

The impact of regional culture on intensive care end of life decision making: an Israeli perspective from the ETHICUS study.

BACKGROUND: Decisions of patients, families, and health care providers about medical care at the end of life depend on many factors, including the societal culture. A pan-European study was conducted to determine the frequency and types of end of life practices in European intensive care units (ICUs), including those in Israel. Several results of the Israeli subsample were different to those of the overall sample. OBJECTIVE: The objective of this article was to explore these differences and provide a possible explanation based on the impact of culture on end of life decision making. METHOD: All adult patients admitted consecutively to three Israeli ICUs (n = 2778) who died or underwent any limitation of life saving interventions between 1 January 1999 and 30 June 2000 were studied prospectively (n = 363). These patients were compared with a similar sample taken from the larger study (ethics in European intensive care units: ETHICUS) carried out in 37 European ICUs. Patients were followed until discharge, death, or 2 months from the decision to limit therapy. End of life decisions were prospectively organised into one of five mutually exclusive categories: cardiopulmonary resuscitation (CPR), brain death, withholding treatment, withdrawing treatment, and active shortening of the dying process (SDP). The data also included patient characteristics (gender, age, ICU admission diagnosis, chronic disorders, date of hospital admission, date and time of decision to limit therapy, date of hospital discharge, date and time of death in hospital), specific therapies limited, and the method of SDP. RESULTS: The majority of patients (n = 252, 69%) had treatment withheld, none underwent SDP, 62 received CPR (17%), 31 had brain death (9%), and 18 underwent withdrawal of treatment (5%). The primary reason given for limiting treatment was that the patient was unresponsive to therapy (n = 187). End of life discussions were held with 132 families (36%), the vast majority of which revolved around withholding treatment (91% of the discussions) and the remainder concerned withdrawing treatment (n = 11, 9%). There was a statistically significant association (chi2 = 830.93, df = 12, p < 0.0001) between the type of end of life decision and region-that is, the northern region of Europe, the central region, the southern region, and Israel. CONCLUSIONS: Regional culture plays an important part in end of life decision making. Differences relating to end of life decision making exist between regions and these differences can often be attributed to cultural factors. Such cultures not only affect patients and their families but also the health care workers who make and carry out such decisions.

Adult↗

PubMed2006

Investigation on stick phenomena in metal-on-metal hip joints after resting periods.

Insufficient understanding of tribological behaviour in total joint arthroplasty is considered as one of the reasons for prosthesis failure. Contrary to the continuous motion input profiles of hip simulators, human locomotion contains motion interruptions. These occurring resting periods can cause stick phenomena in metal-on-metal hip joints. The aim of the present study was to investigate the tribological sensitivity of all-metal bearings to motion interruptions on in vitro test specimens and retrieved implants. Friction and wear with and without resting periods were quantified. Unlike the metal-on-polyethylene joints, the static friction of metal-on-metal joints increased up to micros = 0.3 with rest, while wear appeared to be unaffected. This effect is caused by the interlocking of firmly adhered carbon layers, which were generated from the protein-containing lubricant through tribochemical reactions. Since more than 80 per cent of the retrieved implants exhibited macroscopically visible carbon layers, the increase in friction presumably also occurs under physiological conditions, which is then transferred to the bone-implant interface. These recurrent tangential stress peaks should be considered for the design features of the cup-bone interface, in particular when larger-sized implant heads are used.

Biocompatible Materials↗

PubMed2006

Vaccination with melanoma lysate-pulsed dendritic cells, of patients with advanced colorectal carcinoma: report from a phase I study.

Immune therapy have shown new and exciting perspectives for cancer treatment. Aim of our study was to evaluate toxicity and possible adverse effects from vaccination of patients with advanced colorectal cancer with autologous dendritic cells (DC) pulsed with lysate from a newly developed melanoma cell line, DDM-1.13. Six patients were enrolled in the phase I trial. Autologous DCs were generated in vitro from peripheral blood monocytes in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). DCs were pulsed with melanoma cell lysate from a cloned and selected melanoma cell line enriched in expression of MAGE-A antigens and deficient in expression of melanoma differentiation antigens: tyrosinase, MART-1 and gp100. Vaccinations were administered intradermally on the proximal thigh with a total of five given vaccines at 2 weeks intervals. Each vaccine contained 3-5 x 10(6) DCs. Five of the six patients received all five vaccines. The treatment was well tolerated in all patients without any observed vaccine-correlated adverse effects. Treatment with this DC-based cancer vaccine proved safe and non-toxic.

Adult↗

PubMed2005

[Surgical options for terminal heart failure].

Terminal heart failure can be the cause or the result of major dysfunctions of the organisms. Although, the outcome of the natural history is the same in both situations, it is of prime importance to differentiate the two, as only heart failure as the primary cause allows for successful mechanical circulatory support as bridge to transplantation or towards recovery. Various objective parameters allow for the establishment of the diagnosis of terminal heart failure despite optimal medical treatment. A cardiac index <2.0 l/min, and a mixed venous oxygen saturation <60%, in combination with progressive renal failure, should trigger a diagnostic work-up in order to identify cardiac defects that can be corrected or to list the patient for transplantation with/without mechanical circulatory support.

Assisted Circulation↗

PubMed2005

Compactification of a myelin mimetic Langmuir monolayer upon adsorption and unfolding of myelin basic protein.

The surface shear viscosity of a myelin mimetic Langmuir monolayer is investigated upon adsorption of myelin basic protein (MBP). We measure an increase of the surface shear viscosity at picomolar concentrations of the protein, suggesting that the globular conformation of MBP changes upon adsorption at the monolayer. The conformational change enables hydrodynamic interactions of the proteins, with a typical separation of hundreds of nanometers. This unfolding is essential for the compactification of the myelin sheath, serving an enhanced saltatory signal transduction in vertebrates. The viscometry used extends the sensitivity of standard surface viscometers toward lower viscosities.

Adsorption↗

PubMed2005

Subsurface microstructure of metal-on-metal hip joints and its relationship to wear particle generation.

To control and minimize wear of metal-on-metal hip joints it is essential to understand the mechanisms of debris generation. In vivo, mainly nanosize globular and needle-shaped particles are found. These can neither stem from the action of abrasion nor from tribochemical reactions. In this study the acting wear mechanisms have been first identified on the surface by means of scanning electron microscopy (SEM). Afterwards, the microstructures of the subsurface regions of explants have been investigated using a transmission electron microscope (TEM). Observation of the subsurface gave additional insight about the microstructural changes of cobalt-base alloys subjected to wear. At some distance from the surface, a network of stacking faults and hexagonal epsilon-martensite was found strengthening the bulk material. This microstructure changed into a nanocrystalline type moving closer towards the surface. A comparison of in vivo debris size and grain size of the surface suggests that the globular wear particles result from torn off nanocrystals, while the needle shaped particles are generated by fractured epsilon-martensite. Identified cracks, propagating through the nanocrystalline layer, further support these findings. Thus, it is suggested that the dominating mechanism of particle generation for metal-on-metal joints is surface fatigue within a nanocrystalline surface layer.

Adolescent↗

PubMed2005

Biotic and abiotic degradation behaviour of ethylene glycol monomethyl ether (EGME).

Glycol ethers are widely used in many processes in the chemical industry. Their high water solubility means they are used as solvents for different purposes (e.g. lacquers and varnishes). Since glycol ethers are known to produce toxic metabolites such as the teratogenic methoxyacetic acid during biodegradation, the biological treatment of glycol ethers can be hazardous. However, using oxidizing agents like hydrogen peroxide could be a feasible option for treating wastewater containing glycol ether. In this study, both-, biodegradation and abiotic oxidation experiments with ethylene glycol monomethyl ether (EGME) as contaminant were performed. The biodegradation experiments were conducted with a synthetic model wastewater containing 15 wt% NaCl and 5000 mgl(-1) of EGME. While experiments with the fungus Aspergillus versicolor resulted in the exhaustive biotic degradation of EGME, the toxic metabolite methoxyacetic acid (MAA) was produced as a 'dead end' product. Sodium hydroxide was added to adjust the decreasing pH caused by the production of MAA. In abiotic degradation experiments with EGME, other degradation products--organic acids and toxic aldehydes, e.g. methoxy acetaldehyde (MALD)--were detected. It must be taken into account that EGME and its biotic and abiotic degradation products are usually not analysed in routine wastewater measurements owing to their physical properties.

Acetaldehyde↗

PubMed2005

Hematopoietic stem cell transplantation in severe congenital neutropenia: experience of the French SCN register.

Our objective was to study the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) in patients with severe congenital neutropenia (SCN). Among 101 cases of SCN included in the French Severe Chronic Neutropenia Registry, nine patients received HSCT between 1993 and 2003, in seven institutions. The indications were nonresponse to G-CSF therapy in four cases, bone marrow failure in one case, and myelodysplastic syndrome or leukemia in four cases. The conditioning regimen consisted of total body irradiation in two cases and chemotherapy alone in the other seven cases. Seven patients received stem cells from unrelated donors and two from identical siblings. Engraftment occurred in all but one of the patients. Three patients died. The respective causes of death were graft-versus-host disease, infection, and EBV post-transplant lymphoproliferative disease. Six patients are alive and in complete remission, with a median follow-up of 3.1 years. These results indicate that HSCT is feasible for patients with SCN who do not respond to G-CSF, who have malignant transformation, or who are at a high risk of malignant transformation, even if an HLA-identical sibling donor is not available.

Adolescent↗

PubMed2005

Hematopoietic stem cell transplantation for Shwachman-Diamond syndrome: experience of the French neutropenia registry.

Our objective was to study the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) for Shwachman-Diamond Syndrome (SDS). Among 71 SDS patients included in the French Severe Chronic Neutropenia Registry, 10 received HSCT between 1987 and 2004 in five institutions. The indications were bone marrow failure in five cases, and myelodysplastic syndrome (MDS) or leukemia in five cases. The median follow-up of patients who survived without relapse is 6.9 years (3.1-16.8 years). The conditioning regimen consisted of a busulfan-cyclophosphamide combination (n=6) or total body irradiation plus chemotherapy (n=4). Six patients received stem cells from unrelated donors and four from identical siblings. Engraftment was complete in eight patients and unassessable in two patients. These latter two patients died of infections 32 and 36 days after HSCT, with grade IV graft-versus-host disease and multiorgan dysfunction. A third patient died from an acute respiratory distress syndrome 17 months after HSCT with progressive granulocytic sarcoma. One patient had an MDS relapse 4 months after HSCT and died 10 months later. The overall 5-year event-free survival rate is 60+/-15%. We conclude that HSCT is feasible for patients with SDS who develop bone marrow failure or malignant transformation.

Adolescent↗

PubMed2005

Donor leukocyte infusion after hematopoietic stem cell transplantation in patients with juvenile myelomonocytic leukemia.

Juvenile myelomonocytic leukemia (JMML) is a clonal myeloproliferative disorder of early childhood. In all, 21 patients with JMML who received donor leukocyte infusion (DLI) after allogeneic hematopoietic stem cell transplantation (HSCT) for either mixed chimerism (MC, n=7) or relapse (n=14) were studied. Six patients had been transplanted from an HLA-matched sibling and 15 from other donors. Six of the 21 patients (MC: 3/7 patients; relapse: 3/14 patients) responded to DLI. Response rate was significantly higher in patients receiving a higher total T-cell dose (> or =1 x 10(7)/kg) and in patients with an abnormal karyotype. None of the six patients receiving DLI from a matched sibling responded. Response was observed in five of six patients who did and in one of 15 children who did not develop acute graft-versus-host disease following DLI (P=0.01). The overall outcome was poor even for the responders. Only one of the responders is alive in remission, two relapsed, and three died of complications. In conclusion, this study shows that some cases of JMML may be sensitive to DLI, this providing evidence for a graft-versus-leukemia effect in JMML. Infusion of a high number of T cells, strategies to reduce toxicity, and cytoreduction prior to DLI may improve the results.

Child↗

PubMed2005

Improving immune reconstitution while preventing GvHD in allogeneic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice for many hematologic malignancies and inherited disorders of the hematopoietic system. Ex vivo T-cell depletion (TCD) of the graft and post-transplantation immunosuppression efficiently prevents the development of GvHD in no- MHC-identical settings. However, the consequence of these non-specific strategies is a long-lasting immunodeficiency associated with increased incidence of disease relapse, graft rejection and reactivation of viral infections. Donor lymphocyte infusion, which is used for treating leukemic relapse after allogeneic HSCT, can result in severe GvHD. Several strategies are being optimized specifically to inactivate anti-host T cells while preserving anti-leukemic or anti-microbial immunocompetence. Based on the ex vivo or in vivo elimination of anti-host T cells, or on the modulation of their anti-host activity, these approaches, which have been explored extensively in pre-clinical studies and tested in some preliminary clinical trials, are discussed in this paper.

Clinical Trials as Topic↗

PubMed2005

Transient familial haemophagocytic lymphohistiocytosis reactivation post-CD34 haematopoietic stem cell transplantation.

Familial haemophagocytic lymphohistiocytosis (FHLH) is a genetic disorder caused by defective lymphocyte cytotoxicity, resulting in impaired lymphocyte homeostasis and macrophage infiltration of solid tissues and bone marrow, with extensive haemophagocytosis. It is invariably fatal unless treated by allogeneic haematopoietic stem cell transplantation (HSCT). In a retrospective analysis of 11 cases of FHLH, transplanted in one centre between January 1999 and December 2003, it was found that host T cell expansion occurred early after HSCT in a setting of a viral infection (cytomegalovirus and Epstein-Barr virus respectively) in two cases who received T cell-depleted HSCT. Transient recurrence of clinical and biological manifestations of FHLH was observed, despite evidence for donor cell engraftment. Secondary development of donor T cells led to stable mixed chimaerism and sustained remission of FHLH. Detection of host-derived T cells soon after HSCT in a patient with FHLH should thus not mistakenly be taken as a manifestation of graft rejection.

Antigens, CD34↗

PubMed2005

Chemokine-receptor expression on T cells in lung compartments of challenged asthmatic patients.

BACKGROUND: The interaction of chemokines with their receptors strongly influences the migration of leucocytes. OBJECTIVE: In order to assess the contribution of these molecules to the local recruitment of T cells in bronchial asthma, we analysed the expression of 14 chemokine receptors on lung-derived T cells. METHODS: Chemokine-receptor expression by T cells derived from the peripheral blood, the bronchoalveolar lavage fluid and the bronchial mucosa was analysed by flow cytometry and immunohistochemistry. Expression profiles in healthy and mildly asthmatic individuals were compared, the latter prior and after segmental allergen provocation. RESULTS: Compared with peripheral blood, alveolar T cells expressed significantly more CCR2, CCR5, CCR6, CXCR3 and CCR4. However, no differences were observed between healthy controls and unchallenged asthmatics. In patients developing significant inflammatory responses following specific allergen challenge, a marked increase in the percentage of CCR4+ and CCR7+, and reduced numbers of CXCR3-bearing alveolar T cells were detected. Following specific allergen challenge, chemokine-receptor expression profiles of T cells from the alveolar space and the mucosa or the submucosa were similar, excluding a particular subcompartmentalization of the chemokine/chemokine-receptor system. CONCLUSION: The expression of certain chemokine receptors by lung T cells suggests a contribution to the physiological recruitment of T cells to the lungs, both in healthy controls and unchallenged mild asthmatics. However, strong allergen-induced airway responses were associated with a specific chemokine-receptor profile, suggesting the involvement of certain chemokine receptors in the pathogenesis of allergic bronchial inflammation.

Adult↗

PubMed2005

Allergic airway inflammation induces tachykinin peptides expression in vagal sensory neurons innervating mouse airways.

BACKGROUND: Allergic airway inflammation has been shown to induce pro-inflammatory neuropeptides such as tachykinin peptides substance P (SP) and neurokinin A (NKA) together with related peptide like calcitonin gene-related peptide (CGRP) in nodose sensory neurons innervating guinea-pig airways. OBJECTIVE: The present study was designed to examine the effects of allergen sensitization and challenge on the SP/NKA expression in the jugular-nodose ganglion neurons innervating the murine airways. METHODS: Using retrograde neuronal tracing technique in combination with double-labelling immunohistochemistry, the expression of SP/NKA was investigated in a murine model of allergic airway inflammation. RESULTS: Allergic airway inflammation was found to induce the expression of SP/NKA (13.2+/-1.43% vs. 5.8+/-0.37%, P<0.01) in large-diameter (>20 microm) vagal sensory neurons retrograde labelled with Fast blue dye from the main stem bronchi. CONCLUSION: Based on the induction of tachykinins in airway-specific large-sized jugular-nodose ganglia neurons by allergic airway inflammation, the present study suggests that allergen sensitization and challenge may lead to de novo induction of tachykinins in neurons. This may partly contribute to the pathogenesis of airways diseases such as allergic airway inflammation.

Allergens↗

PubMed2005

Transcriptional up-regulation of histamine receptor-1 in epithelial, mucus and inflammatory cells in perennial allergic rhinitis.

BACKGROUND: Histamine receptors play an important role in the pathogenesis of nasal allergy. Activation of histamine receptor 1 (H1R) and 2 (H2R) can cause allergic symptoms which can be blocked effectively by antihistamines. H1R and H2R transcript levels have been found to be up-regulated in perennial - but not in seasonal - allergic rhinitis (AR). The present study aimed to explore H1R and H2R expression in complex tissues of the nasal mucosa of perennial allergic rhinitis (PAR). METHODS: Ten patients with PAR and 13 non-AR subjects were recruited for the study by medical history, physical examination and laboratory screening tests. In this study, we have analysed single cells dissected from the nasal mucosa biopsies by laser-assisted microdissection. H1R mRNA expression was analysed in different cell types such as epithelial, endothelial, mucus and inflammatory cells isolated from the nasal mucosa of PAR in comparison with non-AR subjects. RESULTS: H1R mRNA gene expression level was significantly increased in the nasal mucosa of PAR in comparison with non-AR (P<0.0001). H1R mRNA was significantly elevated in epithelial (P<0.001) and mucus cells (P<0.05) of PAR in comparison with non-AR whereas H1R gene expression levels in endothelial cells between both groups were not changed (P=0.23). Interestingly, inflammatory cells in the nasal mucosa of PAR patients were also strongly expressed H1R mRNA (P<0.001). CONCLUSION: The present study indicates that PAR alters the expression of H1R mRNA in epithelial, mucus and inflammatory cells of the nasal mucosa and but not in endothelial cells. Therefore, epithelial, mucus and inflammatory cells may play an important role in histamine-mediated allergic airway inflammation in PAR.

Adolescent↗

PubMed2005

Mast cells and vasculature in atopic dermatitis--potential stimulus of neoangiogenesis.

BACKGROUND: Atopic dermatitis skin lesions are characterized by inflammatory changes and epithelial hyperplasia requiring angiogenesis. As mast cells may participate in this process via bidirectional secretion of tissue-damaging enzymes and pro-angiogenic factors, the present study aimed to assess the occurrence and possible function of mast cells in the papillary dermis and in epidermal layers of atopic dermatitis lesions. METHODS: Semi-thin and serial sections in combination with immunohistochemistry, histochemistry and proliferating cell nuclear antigen (PCNA)-activity assays were used and related to epidermal thickness and targeted gene expression studies. RESULTS: Mast cells were located in the papillary dermis and migrated through the basal lamina into the epidermis of atopic dermatitis lesions. An increased PCNA-activity in cells of superficial epidermal layers indicated an activation of keratinocytes and stimulation of endothelial growth. Only approximately 30% of the papillary mast cells stained with the tryptase were toluidin-blue-positive, and approximately 80% were chymase positive. A high number of mast cells expressed c-kit. Most papillary and epidermal mast cells were localized close to endothelial cells. Vascular expression of endoglin (CD105) demonstrated neoangiogenic processes. Mast cells stimulation led to the expression of proangiogenic factors. Also, gene expression of tissue-damaging factors such as matrix metalloproteinases was increased. CONCLUSIONS: These data suggest that in atopic dermatitis, mast cells are abundantly localized close to and within the epidermis where they may stimulate neoangiogenesis. Via the new vessels, inflammatory cells, together with complement components and antibodies, can be transported to the epidermis to aid in the defense against environmental antigens and to maintain chronic inflammation.

Blood Vessels↗

PubMed2005

Henoch-schonlein purpura associated with esophagus carcinoma and adenocarcinoma of the lung.

Henoch-Schönlein purpura (HSP) is known to exist in association with a variety of malignant diseases including squamous and small cell lung cancer and hematological malignancies. We report the first cases of HSP associated with carcinoma of the esophagus and adenocarcinoma of the lung, respectively. We compare the main features of our patients with 23 previously published cases. We recommend that patients with HSP, especially men over 40 years of age, should undergo screening for occult neoplasia.

Adenocarcinoma↗

PubMed2004

Endoscopic management of pancreatic fistulas secondary to intraabdominal operation.

BACKGROUND: Pancreatic fistulas may arise secondary to several disorders of the pancreas. Although approximately 70% of pancreatic fistulas close with nonoperative management, this course of treatment usually takes several weeks or even months. To reduce this long period, closures with fibrin glue have been attempted in the past. In this study, we describe the course, management, and outcome of eight patients with postoperative external pancreatic fistulas of the pancreatic body and tail that arose after oncologic operations in the upper abdomen. METHODS: All eight cases were treated by external drainage, insertion of an endoprosthesis into the pancreatic duct, and closure of the fistula with fibrin glue. RESULTS: Immediately after this intervention, secretion from the fistulas was absent in all cases. None of the patients developed abscesses, recurrent fistulas, or complications associated with the fibrin glue. CONCLUSION: The early endoscopic management of postoperative pancreatic fistula with an approach combining internal drainage of the pancreatic duct and external occlusion of the fistula with fibrin glue is expeditious and beneficial.

Cholangiopancreatography, Endoscopic Retrograde↗